This application relates to implantable biosensors, such as implantable biosensors used for monitoring of blood glucose levels.
Implantable electrochemical biosensors are known for detection of glucose and other analytes found in body fluid. (See, for example, U.S. Pat. Nos. 4,431,004, 6,081,736, 6,119,028, 6,162,611, 6,387,048, 6,466,810, and 7,108,778 and US Patent Publications 20060275859 all of which are incorporated herein by reference). In general, these sensors contain an electrode that is separated from blood or other body fluids by a polymer layer that is permeable to the analyte, but that maintains components such as enzymes that are necessary to the electrochemical detection of the analyte near the surface of the electrode. Analyte diffuses from the blood or body fluid into the polymer layer to be measured. By way of example, measurement of glucose can be performed using the reaction scheme shown in FIG. 1. Glucose is oxidized to gluconolactone in the presence of the enzyme glucose oxidase (GOx). The resulting reduced glucose oxidase is oxidized (and thus reactivated for further reaction with glucose) by oxygen with the resulting production of production peroxide. Peroxide is oxidized at the electrode, and the amount of glucose is reflected in the current generated by this oxidation. A polymer layer is disposed on the electrode to maintain the glucose oxidase in the vicinity of the surface of the electrode.
Error can arise in implantable sensors as a result of variations in the thickness of the polymer layer. Such variations in thickness may arise as a result of manufacturing variations. Variations in the thickness of additional layer that are part of the sensor may also give rise to differences in the observed signal. (See for example U.S. Pat. No. 6,514,718 which is incorporated herein by reference) Furthermore, once an implantable sensor is in use in the body, the surface of the polymer layer may become fouled with proteins or other cellular materials which increase the effective thickness of coating on the electrode and these changes will alter the performance of the electrode. Therefore, unless a correction is made, the error in measurements will increase over time, and the lifetime of the implanted sensor is limited.
The present invention provides for correction for initial variation in thickness of the polymer layer (i.e., manufacturing variation) and for changes in the coating thickness that occur after implantation and therefore provides substantial increase in the accuracy and lifetime of implantable sensors.